Drug Interactions between Adderall and celecoxib / tramadol

MONITOR CLOSELY: The risk of seizures may be increased during coadministration of tramadol with any substance that can reduce the seizure threshold, such as selective serotonin reuptake inhibitors (SSRI antidepressants or anorectics), monoamine oxidase inhibitors, neuroleptic agents, central nervous system stimulants, opioids, tricyclic antidepressants, other tricyclic compounds (e.g., cyclobenzaprine, phenothiazines), carbapenems, cholinergic agents, fluoroquinolones, interferons, chloroquine, mefloquine, lindane, and theophylline. These agents are often individually epileptogenic and may have additive effects when combined. Many of these agents also exhibit CNS- and/or respiratory-depressant effects, which may be enhanced during their concomitant use with tramadol.

MANAGEMENT: Caution is advised if tramadol is administered with any substance that can reduce the seizure threshold, particularly in the elderly and in patients with epilepsy, a history of seizures, or other risk factors for seizures (e.g., head trauma, brain tumor, metabolic disorders, alcohol and drug withdrawal, CNS infections).

MONITOR CLOSELY: The risk of seizures may be increased during coadministration of tramadol with any substance that can reduce the seizure threshold, such as selective serotonin reuptake inhibitors (SSRI antidepressants or anorectics), monoamine oxidase inhibitors, neuroleptic agents, central nervous system stimulants, opioids, tricyclic antidepressants, other tricyclic compounds (e.g., cyclobenzaprine, phenothiazines), carbapenems, cholinergic agents, fluoroquinolones, interferons, chloroquine, mefloquine, lindane, and theophylline. These agents are often individually epileptogenic and may have additive effects when combined. Many of these agents also exhibit CNS- and/or respiratory-depressant effects, which may be enhanced during their concomitant use with tramadol.

MANAGEMENT: Caution is advised if tramadol is administered with any substance that can reduce the seizure threshold, particularly in the elderly and in patients with epilepsy, a history of seizures, or other risk factors for seizures (e.g., head trauma, brain tumor, metabolic disorders, alcohol and drug withdrawal, CNS infections).

MONITOR: Coadministration with inhibitors of CYP450 2D6 may increase the plasma concentrations as well as the pharmacologic and adverse effects of amphetamines. The proposed mechanism involves the inhibition of CYP450 2D6, an isoenzyme partially responsible for the metabolic clearance of certain amphetamines. Furthermore, because CYP450 2D6 is genetically polymorphic, variations in amphetamine metabolism across populations may either increase or decrease the risk associated with this interaction. Increased exposure to amphetamines may potentiate the risk of serious adverse reactions such as serotonin syndrome, seizures, psychiatric adverse reactions (e.g., new psychotic or manic symptoms), peripheral vasculopathy (including Raynaud's Phenomenon), and cardiovascular effects (e.g., hypertension, tachycardia). However, data evaluating the interaction are not available.

MANAGEMENT: Caution and closer monitoring for adverse effects are recommended when amphetamines are used concurrently with CYP450 2D6 inhibitors, and a reduction in the initial amphetamine dose should be considered. Patients should be more closely monitored for signs and symptoms of serotonin syndrome, particularly during the initiation of amphetamine therapy and following any dosage increases. Additional caution is advised when amphetamines are coadministered with CYP450 2D6 inhibitors that lower the seizure threshold (e.g., bupropion). Patients should be instructed to notify their healthcare provider if they experience increased amphetamine-related side effects, such as seizures, cardiovascular effects (e.g., hypertension, tachycardia), or symptoms of serotonin syndrome (e.g., mental status changes, autonomic dysfunction like tachycardia or hyperthermia, neuromuscular abnormalities such as hyperreflexia, or gastrointestinal symptoms).

MONITOR: Coadministration with inhibitors of CYP450 2D6 may increase the plasma concentrations as well as the pharmacologic and adverse effects of amphetamines. The proposed mechanism involves the inhibition of CYP450 2D6, an isoenzyme partially responsible for the metabolic clearance of certain amphetamines. Furthermore, because CYP450 2D6 is genetically polymorphic, variations in amphetamine metabolism across populations may either increase or decrease the risk associated with this interaction. Increased exposure to amphetamines may potentiate the risk of serious adverse reactions such as serotonin syndrome, seizures, psychiatric adverse reactions (e.g., new psychotic or manic symptoms), peripheral vasculopathy (including Raynaud's Phenomenon), and cardiovascular effects (e.g., hypertension, tachycardia). However, data evaluating the interaction are not available.

MANAGEMENT: Caution and closer monitoring for adverse effects are recommended when amphetamines are used concurrently with CYP450 2D6 inhibitors, and a reduction in the initial amphetamine dose should be considered. Patients should be more closely monitored for signs and symptoms of serotonin syndrome, particularly during the initiation of amphetamine therapy and following any dosage increases. Additional caution is advised when amphetamines are coadministered with CYP450 2D6 inhibitors that lower the seizure threshold (e.g., bupropion). Patients should be instructed to notify their healthcare provider if they experience increased amphetamine-related side effects, such as seizures, cardiovascular effects (e.g., hypertension, tachycardia), or symptoms of serotonin syndrome (e.g., mental status changes, autonomic dysfunction like tachycardia or hyperthermia, neuromuscular abnormalities such as hyperreflexia, or gastrointestinal symptoms).

MONITOR: Coadministration with celecoxib may increase the plasma concentrations of drugs that are substrates of the CYP450 2D6 isoenzyme. The mechanism is decreased clearance due to inhibition of CYP450 2D6 activity by celecoxib.

MANAGEMENT: Caution is advised if celecoxib must be used concurrently with medications that undergo metabolism by CYP450 2D6, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever celecoxib is added to or withdrawn from therapy.